Long-Term Objectives: Transposable genetic elements are ubiquitous in eukaryotic genomes. The goal is to understand how such elements are able to insert into new genomic positions, excise from old ones, and regulate these activities. Specific Aims: Transposition: Some transposable elements transpose by replicating themselves in new positions, whereas others jump "conservatively", with the donor site being deleted in the process. Proposed experiments will determine the mechanism of mobility for the P family of transposable elements in Drosophila melanogaster. Regulation: Some P elements are known to produce a gene product that regulates their own mobility. Experiments will determine the genetic requirements for this regulation and its relationship to the element's gene expression. Health Relatedness: Transposable element insertions are thought to be a major source of spontaneous mutations. These experiments will provide the basic data on how P elements function, and thus contribute to the understanding of the rate and control of harmful mutations. In addition, P elements are widely used as genetic vectors for studying general questions of gene function. Results of the proposed experiments can be used to enhance these techniques. Finally, it is thought that insect transposable elements will eventually prove useful in fighting insect pests. An understanding of their basic biology, as will be obtained from these experiments, will be essential for any such effort. Methods: A combination of standard genetic and molecular techniques will be employed. Drosophila will be cultured in the laboratory and screened by phenotype for the genetic variations of interest. Molecular techniques include DNA sequencing and polymerase chain reaction for amplification of specific DNA se-